Ingrid V. Sils

Hyperthermia-induced changes in the vascular permeability of rats: a model system to examine therapeutic interventions.

Extravasation in the heart, liver, lung, kidney, spleen, gastrocnemius, and duodenum was quantified in normothermic and hyperthermic (core temperature (T(c))=41.5, 42, or 42.6 degrees C) rats. Following attainment of the target T(c), Evans blue (Eb) was administered via jugular cannula; the animals were anesthetized, exsanguinated, tissues removed and washed in saline, and Eb extracted with formamide. There was significantly (p<0.05) more Eb (µg/g of dry wt of tissue, mean+/-SD) in the tissues of severely hyperthermic (T(c)=42.6 degrees C) rats vs that of control rats: liver - 198+/-39 vs 125+/-28, kidney - 376+/-68 vs 176+/-60, and small intestine - 170+/-49 vs 106+/-20. This model may be useful in evaluating the efficacy of treatment modalities designed to sustain vascular integrity in the face of environmental insult.

Hyperthermic effects on reticuloendothelial system particulate uptake.

Reticuloendothelial system (RES) particulate uptake (PU) of vascular debris influences survival from extreme hyperthermia. Little is known of the effect of extreme hyperthermia, unrelated to fever, on RES PU shortly after reaching a maximum core temperature (T(c)). Relative to normothermic rats (T(c)=38.0 degrees C), rats at T(c)=42.6 degrees C had significantly higher, while T(c)=42.0 degrees C rats had significantly lower total RES tissue (lung, liver, spleen) PU of fluorescent microspheres (1 µ), when compared to rats at T(c)=42.6 or 38.0 degrees C. These findings suggest at T(c)=42.6 degrees C, rats were not actively thermoregulating. As such, more blood remained in the core than in the periphery, which resulted in greater core RES tissue PU. In contrast, to reduce or control core heat, rats at T(c)=42.0 degrees or 38.0 degrees C directed more blood to the periphery, which reduced core RES tissue PU. Blood flow patterns as directed by the state or degree of active thermoregulation is likely an influence of hyperthermia on RES PU.

Treatment of hyperthermia-induced extravasation with hypertonic saline (7.5%) in 6% dextran 70 (HSD) in Wistar/Furth rats.

This study determined the effectiveness of hypertonic saline (7.5%) in 6% Dextran 70 (HSD) in reducing hyperthermia-induced extravasation in Wistar/Furth (WF) rats and compared this extravasation with that previously reported in Sprague-Dawley (SD) rats. Wistar/Furth rats (male, n = 12/group, 300-325 g) were placed unrestrained in a chamber (41.5 degrees C) until a core temperature (Tc) of 42.6 degrees C was attained. Immediately following heat exposure, HSD or normal saline (4 mL/kg) was administered via jugular catheter, followed 15 min later by Evans blue (Eb, 25 mg/kg) in normal saline. After another 15-min interval, animals were anesthetized, exsanguinated, tissues removed and washed in normal saline, and Eb was extracted with formamide. Another group of normothermic WF rats were also given Eb and had tissues harvested. Comparisons were made to extravasation in normothermic and hyperthermic SD rats. In hyperthermic SD rats, Eb content increased significantly in liver, kidney, and intestinal tissues. In hyperthermic WF rats compared to normothermic WF rats, Eb content of kidney and spleen was increased; however, Eb content of heart, skeletal muscle, and intestine was significantly decreased. HSD-treated WF rats had increased extravasation in intestinal tissue compared to that of saline-treated rats. However, HSD treatment resulted in significant decreases in wet weight/dry weight ratios of heart (4.34 +/- 0.10 versus 4.51 +/- 0.11) and skeletal muscle tissue (3.78 +/- 0.08 versus 3.91 +/- 0.08). Findings of this study indicate that HSD did not prevent the hyperthermia-induced extravasation of Eb in kidney and spleen; that the increase in plasma volume following HSD administration is most likely due to the movement of fluid into the vasculature from the skeletal muscle mass; and that the WF strain may have limited value for the study of extravasation.